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Defining Glutaric Acidemia Type II

GA2 is a form of inherited disorder that interferes with a person's body and its ability to break down fats and proteins in order to produce energy. Fats and proteins that are not processed completely may build up in the person's body, causing their tissues and blood to become too acidic, something referred to as, 'metabolic acidosis.' GA2 commonly appears while the person is still in infancy, or during early childhood. The person usually experiences a metabolic crisis during which low blood sugar and acidosis causes weakness and behavioral changes. The behavioral changes can include vomiting, a decrease in activity, as well as poor feeding. The metabolic crisis may actually be life-threatening and can be triggered by common forms of childhood illnesses or other stresses.

People who are affected most severely by GA2 might also be born with physical abnormalities that include enlargement of the liver or, 'hepatomegaly,' brain malformations, or enlargement and weakening of their heart, referred to as, 'dilated cardiomyopathy.' They may be born with unusual facial features, genital abnormalities, or fluid-filled cysts. GA2 may also cause the person affected by the disorder to present with a characteristic odor that resembles sweaty feet.

On the opposite end, some persons are affected with less severe symptoms of the disorder that start later in their childhood, or even in adulthood. People affected by milder forms of GA2 experience muscle weakness that develops in adulthood as a first sign of the disorder. GA2 is an exceptionally rare disorder that has been reported in a number of different ethnic groups.

GA2 is a form of autosomal recessive disorder, meaning that both of the affected person's parents must be carriers of the disorder and the gene for it. When the both of the genes combine, their child will be born with GA2. Each of the children from parents who carry the gene for GA2 has a twenty-five percent chance of inheriting the disorder.

People with GA2 have a protein in their body, an inactive enzyme. There are two specific enzymes that can be associated with GA2; both of them have functions that are similar in the person's body. People with GA2 might lack either of them. These enzymes are Electron Transfer Flavoprotein (ETF), and ETF-ubiquinone oxidoreductase (ETF: QO). Both of these enzymes may be found in a number of cells within the person's body. They play important roles in the breakdown of proteins and fats, as well as assisting to produce energy. The enzymes help with important functions in the person's body, functions that help them to remain healthy.

Causes

Mutations in any one of the genes: ETFA, ETFDH, or ETFB, may result in glutaric acidemia type II (GA2). Both the ETFB and ETFA genes provide instructions for the production of two gene segments that combine to create an enzyme referred to as, 'electron transfer flavoprotein.' The ETFDH gene provides instructions for the creation of an enzyme referred to as, 'electron transfer flavoprotein dehydrogenase.' GA2 is caused by a deficiency in these enzymes. Electron transfer flavoprotein and electron flavoprotein dehydrogenase are usually active in a person's mitochondria, the energy-producing centers of their cells. The enzymes assist in breaking down fats and proteins in order to provide energy for the person's body. Should one of these enzymes be either defective or missing, nutrients that are partially broken down accumulate in the person's cells, damaging them, and cause the signs and symptoms of GA2.

People with GA2 and the resulting gene mutations which result in a complete loss of either enzyme that is produced from the ETFA, ETFB, or ETFDH genes will probably experience the most severe symptoms associated with the disorder. Mutations that permit the enzymes to function at some level can result in milder forms of GA2. The disorder is also known by other names, to include:

GA II

EMA

MAD

MADD

ETFA deficiency

ETFB deficiency

ETFDH deficiency

Glutaric aciduria, type 2

Glutaric acidemia, type 2

Ethylmalonic-adipicaciduria

Electron transfer flavoprotein deficiency

Multiple FAD dehydrogenase deficiency

Multiple acyl-CoA dehydrogenase deficiency

Symptoms of Glutaric Acidemia Type II

People with GA2 can experience nonketotic hypoglycemia, heart disease, acidosis, vomiting, nausea, weakness, lethargy, and enlargement of their liver. Stress, through a virus or exercise, can cause a person with GA2 to experience periods of low blood sugar. Hypoglycemia experienced by persons with GA2 can be severe, making them shaky, weak, and dizzy.

The less severe form of GA2 is referred to as, 'late onset glutaric acidemia type II.' The age of onset can be extremely variable for people with this form of GA2. People affected by late onset GA2 experience the disorder to varying degree. Children with the disorder might not experience symptoms until they are several years old. Some may not experience any symptoms until they have reached adulthood.

There is a form of GA2 that is referred to as, 'neonatal glutaric acidemia type II.' Newborns who develop symptoms of this form of GA2 during the first days of their lives many times do not survive for more than a few weeks or months, unfortunately. The symptoms of the neonatal form of GA2 are severe.

Diagnosing

GA2 is a disorder that can be easily recognized in newborns who experience a complete deficiency of ETF or ETF: QO, demonstrated through an abnormal pattern of organic acids in their urine. It is; however, more difficult to achieve a diagnosis in children who experience incomplete defects because the features they experience might be varied or episodic. The organic acids in their urine might present as abnormal, or even slightly abnormal, only when they are very sick. Achievement of a GA2 diagnosis can be further complicated by the fact that similar organic acid urine changes might be witnessed in deficiency of riboflavin, as well as when infants consume formulas that contain medium-chain triglycerides, something that is common.

The presence of an increase in certain carnitine esters in a child's blood may suggest GA2 although, as in urine organic acids, this might be due to riboflavin deficiency. Studies related to fibroblasts that have been grown from skin biopsies might be the best way to achieve a diagnosis because nutrition does not influence them. There are laboratories that test for GA2 and are capable of achieving a diagnosis of the disorder.

Treatment of Glutaric Acidemia Type II

Late onset GA2 is currently being treated through a diet that is low in protein and fat, while being high in carbohydrates. What this means is that people who experience the disorder should consume foods with very little protein or fats in them because their bodies do not have the enzymes needed to break these elements down properly. People with late onset GA2 should consume lots of carbohydrates instead of proteins and fats so they have enough calories for energy. Eating at regular and consistent intervals is recommended in order to avoid fasting and the potential for low blood sugar levels that might trigger a metabolic crisis. A metabolic nutritionist has the potential to help people with GA2 and their family members with development of meal planning that meet the affected person's needs. L-carnitine and riboflavin supplements are also recommended for persons with mild or late onset GA2.

Family members play an important role in the effective treatment of their loved one with GA2. Siblings and other family members, as well as children with GA2, need to learn about the unique dietary considerations associated with the disorder early on. It is also important that people who will come in contact with the person who has GA2, such as relatives, babysitters, or teachers, learn the signs to look for in relation to a crisis. It is important that these people have an emergency protocol sheet available to them so they are prepared if an emergency should occur.

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